T-lymphocytes play a major role in the immune response by interacting with target and antigen presenting cells. For example, the T-lymphocyte mediated killing of target cells is a multi-step process involving adhesion of a cytolytic T-lymphocyte to a target cell. And, helper T-lymphocytes initiate the immune response by adhesion to antigen-presenting cells.
These interactions of T-lymphocytes with target and antigen-presenting cells are highly specific and depend on the recognition of an antigen on the target or antigen-presenting cell by one of the many specific antigen receptors on the surface of the T-lymphocyte.
The receptor-antigen interaction of T-lymphocytes and other cells is also facilitated by various T-lymphocyte surface proteins, e.g., the antigen receptor complex CD3(T3) and accessory molecules CD4, LFA-1, CD8, and CD2. It is also dependent on accessory molecules, such as LFA-3, ICAM-1 and MHC that are expressed on the surface of the target or antigen-presenting cells. In fact, it is hypothesized that the accessory molecules on the T-lymphocytes and on the target or antigen-presenting cells interact with each other to mediate intercellular adhesion. Accordingly, these accessory molecules are thought to enhance the efficiency of lymphocyte-antigen-presenting cell and lymphocyte-target cell interactions and to be important in leukocyte-endothelial cell interactions and lymphocyte recirculation.
For example, recent studies have suggested that there is a specific interaction between CD2 (a T-lymphocyte accessory molecule) and LFA-3 (a target cell accessory molecule) that mediates T-lymphocyte adhesion to the target cell. This adhesion is essential to the initiation of the T-lymphocyte functional response (M. L. Dustin et al., "Purified Lymphocyte Function-Associated Antigen-3 Binds To CD2 And Mediates T Lymphocyte Adhesion, J. Exp. Med., 165, pp. 677-92 (1987); Springer et al., Ann. Rev. Immunol. (1987) (in press)). And, monoclonal antibodies to either LFA-3 or CD2 have been shown to inhibit a spectrum of cytolytic T lymphocyte and helper T lymphocyte dependent responses (F. Sanchez-Madrid et al., "Three Distinct Antigens Associated With Human T-Lymphocyte-Mediated Cytolysis: LFA-1, LFA-2, And LFA-3", Proc. Natl. Acad. Sci. USA, 79, pp. 7489-93 (1982)).
LFA-3 is found on antigen-presenting cells, and target cells, specifically on monocytes, granulocytes, CTL's, B-lymphoblastoid cells, smooth muscle cells, vascular endothelial cells, and fibroblasts (Springer et al., supra).
Human LFA-3 has been purified from human erythrocytes (Dustin et al., supra). It is a glycoprotein of 60,000 to 70,000 molecular weight, having a sugar content of about 50%. This purified LFA-3 binds to CD2 on the surface of T-lymphocytes and inhibits adhesion between T-lymphocytes and erythrocytes (Dustin et al., supra).
However, for ultimate use in therapy and diagnosis larger amounts of less costly LFA-3 are required than would be available from purification from erythrocytes. Moreover, for therapeutic use it would be more preferable to obtain LFA-3 from a source other than human erythrocytes, which may be contaminated with viruses, such as hepatitis B viruses or AIDS viruses.